Comparison of Renal Biomarkers with Glomerular Filtration Rate in Susceptibility to the Detection of Gentamicin-Induced Acute Kidney Injury in Dogs

Sasaki, Akira; Sasaki, Yui; Iwama, Ryosuke; Shimamura, Shunsuke; Yabe, Koichi; Takasuna, Kiyoshi; Ichijo, Toshihiro; Furuhama, Kazuhisa; Satoh, Hiroshi

doi:10.1016/j.jcpa.2014.06.001

Cited by 32 publications

(25 citation statements)

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“…18 Remarkably, significant increases in Ur CYS C concentrations and reductions in eGFR levels were detected on D4 and termination in the absence of relevant changes in sCr, BUN concentrations and/or other urine-based parameters. 18 Remarkably, significant increases in Ur CYS C concentrations and reductions in eGFR levels were detected on D4 and termination in the absence of relevant changes in sCr, BUN concentrations and/or other urine-based parameters.…”

Section: Discussionmentioning

confidence: 89%

“…A hallmark DIKI biomarker study in male beagle dogs treated by intravenous infusion with the nephrotoxic chemotherapeutic agent/tubular nephrotoxicant, CDDP (0.75 mg per kg per dose, single iv infusion for 5 consecutive days) was published. 8,18 This study was conducted in the context of the C-Path's PSTC NWG to evaluate the performance of various dog-specific enzyme immunoassay reagents intended for biomonitoring for DIKI in male beagle dogs using CDDP as a model nephrotoxicant. Increased sCr levels, indicative of a substantial loss of GFR in CDDP-treated dogs were not observed until approximately D16.…”

Section: Introductionmentioning

confidence: 99%

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Cisplatin nephrotoxicity in male beagle dogs: next-generation protein kidney safety biomarker tissue expression and related changes in urine

et al. 2016

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This 10-day (D) study was conducted to evaluate changes in traditional and newer kidney safety biomarker expression levels in dogs. Animals received cisplatin (CDDP, 0.75 mg per kg per day) or 0.9% Saline (vehicle) for 5 days. Serum/urine samples were collected at various time points. Cage-side observations included emesis (D1-2/D4-D5/D7-9), absence of stool (D5-9/D11), soft stool (D4-7/D12), excessive salivation (D1/D3/D5-6), decreased food consumption (D5-8), decreased activity (D7-8) and/or dehydration (D7). Animals were necropsied when serum creatinine (sCr) levels measured at ≥1.9 mg dL, indicating significant loss of renal function; or at the end of the study (D11). When compared to controls, increases in BUN/sCr were detected on D3, D5 and/or D8. Increases in urinary total protein (Ur TP) were noted on D6. The moribund dog that was euthanized early on D7 showed insignificant increases in urinary osteopontin (Ur OPN), urinary neutrophil gelatinase-associated lipocalin (Ur NGAL), urinary clusterin (Ur CLU), sCr, serum cystatin C (sCYS C) and urinary cystatin C (Ur CYS C) on D5 when compared to controls. Insignificant increases in urinary albumin (Ur ALB) were observed from an animal that was euthanized on D7 and 1 : 2 surviving animals on D8 relative to baseline. From three dogs that were euthanized on D9, increases in Ur CLU, and/or sCYS C were noted on D8 relative to baseline. The two surviving dogs showed elevated Ur CLU and 1 : 2 surviving dogs showed elevated Ur CYS C. Decreased urinary kidney injury molecule 1 (Ur KIM-1) on D3/D5 was evident ( baseline and controls). CDDP-induced cortico-medullary lesions were characterized as minimal to mild tubule degeneration/necrosis, dilatation, regeneration, cell alteration, intratubular casts, interstitial inflammation and vacuolization. Increased Ur OPN and Ur CLU correlated with enhanced OPN and CLU immunopositive staining in damaged cortical epithelium in the proximal tubules. Enhanced KIM-1 staining in damaged cortico-medullary tubular epithelium appeared in the absence of rises in Ur KIM-1. This study showed changes in kidney safety protein biomarkers associated with CDDP nephrotoxicity in dogs and possibly in humans.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Cisplatin nephrotoxicity in male beagle dogs: next-generation protein kidney safety biomarker tissue expression and related changes in urine

et al. 2016

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“…In addition to human, L‐FABP expression in the kidneys was reported only in rats . Previous studies examined urinary excretion of L‐FABP in dogs and pigs, but they did not show the renal expression of L‐FABP. Because L‐FABP expresses not only kidneys but also other tissues such as the liver, pancreas, and small intestine, it is necessary to examine the renal expression of L‐FABP in each species.…”

Section: Discussionmentioning

confidence: 99%

Renal expression and urinary excretion of liver‐type fatty acid‐binding protein in cats with renal disease

Katayama

Ohata

Miyazaki

et al. 2020

Veterinary Internal Medicne

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Background Liver‐type fatty acid‐binding protein (L‐FABP) is a biomarker for early detection of renal disease in humans. Liver‐type fatty acid‐binding protein is cytotoxic oxidation products secreted from proximal tubules under ischemia and oxidative stress. Objective To examine renal expression and quantify urinary excretion of L‐FABP in catswith renal disease. Animals One hundred and thirty‐four client‐owned cats including 34 cats with serum creatinine (sCre) values >1.6 mg/dL and 10 other cats that died in clinics. Methods Tissue expressions of L‐FABP were examined by reverse transcription polymerase chain reaction and Western blotting. Urinary L‐FABP (uL‐FABP) and serum L‐FABP (sL‐FABP) levels were determined by enzyme‐linked immunosorbent assay. Anti‐liver‐type fatty acid‐binding protein antibody immunostained renal sections. Results Feline kidneys express L‐FABP. Strong L‐FABP signals were observed in the lumens of proximal tubular cells in 5 cats with high uL‐FABP excretion, but not in 5 cats with low uL‐FABP excretion. In 9 normal cats, uL‐FABP index was <1.2 μg/g urinary creatinine (uCre). High uL‐FABP indexes (>10.0 μg/g uCre) were detected in 7 of 100 cats with low sCre (<1.6 mg/dL) and 18 of 44 cats with high sCre (>1.6 mg/dL). There was a weak correlation between L‐FABP index and sCre, serum symmetric dimethylarginine (SDMA), or blood urea nitrogen (BUN), and these correlation coefficients were increased by analyzing only data of cats with sCre >1.6 mg/dL. There was a weak correlation between u L‐FABP index and sL‐FABP in all tested cats, but not in cats with high sCre. Conclusions and Clinical Importance This study demonstrates correlations between L‐FABP and current renal biomarkers for chronic kidney disease in cats, such as sCre and SDMA. Liver‐type fatty acid‐binding protein may be a potential biomarker to predict early pathophysiological events in feline kidneys.

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“…Treiber M and collaborates stated that cystatin C was a better marker than creatinine in neonatals to determine acute renal damage after perinatal hypoxia/asphyxia [26]. Similar results were found in animal experiments and also in the studies which were made with adults [27,28]. There are very few articles which assess renal functions in children who are exposed to acute mercury.…”

Section: Discussionmentioning

confidence: 69%

Assessment of renal functions with different glomerular filtration rate formulas in children with acute exposure of mercury

Bal

Güngör

Çelik

et al. 2015

Turkish Journal of Biochemistry

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Objective: Our aim was to determine whether cystatin C level has a superiority to creatinine to assess kidney functions in rapid decreases of glomerular filtration rate due to acute mercury exposure in children. Eight different glomerular filtration rate calculation formulas which have been used creatinine and/or cystatin C were also compared.Methods: Serum urea, creatinine and cystatin C values of 39 mercury exposed children were measured. Glomerular filtration rates were calculated by eight different formulas. Patient group was divided into three subgroups according to mercury levels.Results: Cystatin C and mercury levels of the patients were found significantly different from control group (p<0.001). There was not a significant difference in creatinine and urea values between two groups (p=0.913, p=0.236). There was not a significant difference between patient and control groups in GFR calculations which have been used serum creatinine and height or which have been used urea additional to them (p=0.069, p=0.559, p=0.424, p=0.945, respectively), but there was a significant difference between patient and control groups in GFR calculations which have been used cystatin C only or creatinine, urea and height in addition to this (p<0.001, p<0.001, p=0.042, p<0.001, respectively). In sugroup analysis, cystatin C results and the results of three GFR calculations of four GFR calculations which were used cystatin C were found different in control group according to subgroups but there was not a difference between subgroups.Conclusion: Cystatin C level is a better indicator than creatinine to assess kidney functions in rapid decreases of glomerular filtration rate due to acute exposure of mercury. Formulas using cystatin C gave better results than formulas using creatinine and height in estimation of glomerular filtration rate.Özet: Amaç: Çocuklarda akut civa maruziyetine bağlı hızlı glomerüler fitrasyon hızı azalmalarında sistatin C düze-yinin böbrek fonksiyonlarını değerlendirme açısından Ceylan Bal et al.: Children with acute exposure of mercury 259 kreatinine üstün olup olmadığını belirlemeyi amaçladık. Ayrıca kreatinin ve/veya sistatin C kullanılan 8 ayrı glomerular filtrasyon hızı hesaplama formülünü birbiriyle karşılaştırdık.Metod: Civa maruziyeti yaşayan 39 çocuğun serum üre, kreatinin ve sistatin C düzeyleri ölçüldü. Glomerular filtrasyon hızı 8 farklı formülle hesaplandı. Hasta grubu civa seviyelerine göre üç subgruba bölündü. Bulgular: Hastaların sistatin C ve civa düzeyleri kontrol grubundan anlamlı olarak farklı bulundu (p<0.001). Kreatinin ve üre açısından iki grup arasında anlamlı bir fark bulunmadı (p=0.913, p=0.236). Serum kreatinini ve boy kullanılarak veya bunlara ilaveten üre değerleri kullanıla-rak yapılan GFR hesaplamalarında hasta ve kontrol grupları arasında anlamlı bir fark yokken (sırasıyla, p=0.069, p=0.559, p=0.424, p=0.945 ), yalnızca sistatin C veya buna ek olarak kreatinin, üre ve boyun kullanıldığı GFR hesaplamalarında hasta ve kontrol grupları arasında anlamlı bir fark vardı (sırasıyla, ...

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Comparison of Renal Biomarkers with Glomerular Filtration Rate in Susceptibility to the Detection of Gentamicin-Induced Acute Kidney Injury in Dogs

Cited by 32 publications

References 23 publications

Cisplatin nephrotoxicity in male beagle dogs: next-generation protein kidney safety biomarker tissue expression and related changes in urine

Cisplatin nephrotoxicity in male beagle dogs: next-generation protein kidney safety biomarker tissue expression and related changes in urine

Renal expression and urinary excretion of liver‐type fatty acid‐binding protein in cats with renal disease

Assessment of renal functions with different glomerular filtration rate formulas in children with acute exposure of mercury

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